The basal ganglia-habenula circuitry in reward processing the overall goal of this project is to investigate the basic brain mechanisms underlying reward processing. Recent studies demonstrate that the lateral habenula (LHb) provides valence signals to the midbrain dopamine areas. However, in part owing to the challenges in monitoring and manipulating activities in the LHb circuitry, the roles of this circuiry in more complex behaviors still remain elusive. In particular, how LHb neurons acquire the valence signals, and whether and how these signals are used to guide behavior, are questions that remain unresolved. Bridging these gaps is of great clinical significance, because LHb dysfunction is implicated in the pathogenesis of depression, a major psychiatric disorder in which deficit in reward processing is the hallmark. In the proposed study, we plan to approach these questions by investigating how functionally distinct groups of neurons in the basal ganglia-lateral habenula circuitry coordinate and participate in reward processing, thereby influencing behavior. For this purpose we have devised an integrated strategy that combines molecular genetic tools together with electrophysiological, imaging, optogenetic, chemogenetic, and behavioral techniques. Findings from this research program will provide novel insight into the synaptic, cellular, and circuit mechanisms by which the basal ganglia-lateral habenula circuitry contributes to reward-related processes.